Time course of ERK, MSK1, and histone H3 phosphorylation in D1R-striatonigral neurons after a single exposure to cocaine. A, B, EGFP fluorescence (green), p-ERK immunofluorescence (red), and p-MSK1 (blue, top) or p-H3 (blue, bottom) immunofluorescence in the dorsal striatum (DStr; A) and the NAc shell (B) of drd1a-EGFP mice. Arrowheads point to D1R-positive neurons that contain both p-ERK and p-MSK1 or p-H3. Photographs are single confocal sections. Scale bars, 40 μm. C–E, Percentage of EGFP-positive neurons immunoreactive for p-ERK (red, left y-axis), p-MSK1 (blue, right y-axis), and p-H3 (green, right y-axis) at various times after cocaine injection in drd1a-EGFP mice, in a different set of experiments from those in A and B: dorsal striatum (C), NAc shell (Shell; D), and NAc core (Core; E). Data (means ± SEM; n = 3–4 mice per group) were analyzed using one-way ANOVA (values in supplemental Table 3, available at www.jneurosci.org as supplemental material). Filled circles, p < 0.05, groups 2–60 min versus 0 min (Dunnett's multiple test); open circles, not significant.